ABSTRACT

Myeloproliferative neoplasms (MPNs) represent a heterogeneous range of clonal hematopoietic stem cell diseases that can be subdivided into classic and nonclassic myeloproliferative disorders (Table 26.1) [1–13]. Classical myeloproliferative disorders include chronic myeloid leukemia (CML) and three major non-CML categories: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Nonclassical myeloproliferative disorders include chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), hypereosinophilic syndrome (HES), systemic mastocytosis (SM), chronic basophilic leukemia, atypical CML, chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), 8p11 myeloproliferative syndrome (EMS), and myeloproliferative disorders, not otherwise classified (which include refractory anemia with ring sideroblasts and thrombocytosis, among others). Diagnostic workup of MPN is presented in Figure 26.1. Classification of MPNs https://www.niso.org/standards/z39-96/ns/oasis-exchange/table">

MPN

Molecular/Cytogenetics Characteristics

Classical

CML

BCR–ABL [t(9;22)]; 100%

PV

JAK2 V617F; ~95%

JAK2 V617F; ~40%–50%

ET

JAK2 exon 12 mutations; ~5%

MPL W515L/K; ~1%

PMF

JAK2 V617F; ~50%

MPL W515L/K; ~5%

Nonclassical

CNL

Normal cytogenetics; ~80%

JAK2 V617F; rare cases

CEL, not otherwise specified (CEL, NOS)

No BCR–ABL fusion; no PDGFRA, PDGFRB, or FGFR1 rearrangement; clonality of eosinophils or increased blasts (6%–19% in the BM) required for diagnosis

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1

FIP1L1–PDGFRA fusion; or t(5;12)(q31–33;p12) or variant translocation, or demonstration of an ETV6–PDGFRB fusion gene (or of the rearrangement of PDGFRB)

HES

No clonal cytogenetic or molecular changes; blasts <5% in the BM; eosinophilia >1.5 × 109/L for ≥6 months

SM

KIT D816V; ~90%

Chronic Basophilic Leukemia

Atypical CML

JAK2 V617F; ~20%

MPN, unclassifiable

JAK2 V617F; ~20%–50%; no BCR–ABL fusion

Algorithm for the diagnosis of classical MPNs. https://s3-euw1-ap-pe-df-pch-content-public-u.s3.eu-west-1.amazonaws.com/9780429170478/da7043d1-f22d-431e-b5ce-d16b7eec9abc/content/fig26_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>